Results from the prior grant period using electrophysiological recordings support the hypothesis that patients with CFS have a disorder of central motor control. Moreover, recent studies by others using transcranial magnetic stimulation also point to the central auditory pathway as being abnormal in CFS. The patients in our studies showed slowed reaction times in tasks requiring rapid responses and impaired brain activities accompanying motor response preparation. Transcranial magnetic stimulation has demonstrated a premature reduction of motor cortical output in CFS accompanying sustained motor activities. Our goals in the proposed new project are to define the time course of altered motor cortical function in CFS before and after a period of exercise-induced fatigue. The specificity of the abnormalities for CFS will be tested by comparison with a group of patients with clinical depression. The methods of study utilize neurophysiological recordings of slow brain potentials accompanying several different types of response preparation and transcranial magnetic stimulation of motor cortex to measure the extent of reduction of central motor drive.